Introduction to DMF

Bhupendra Sharmahttps://cz.linkedin.com/in/bhuppi1986

Introduction to CTD

• NTA-V-II• EU Validation criteria 6.1

DMF• A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used

to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.

• not required by law or FDA regulation. • submitted solely at the discretion of the holder. • Submitted for support

• Two parts :

(1) Applicant’s Part: This contains non confidential information that the license holder needs to assess for the marketing.

(2) Restricted Part: This contains confidential information about the manufacturing procedure that only needs to be disclosed to the authorities.

How the US DMF System Works:• Filing the DMF

• Holder sends two copies of the DMF to FDA• DMF is reviewed for administrative purposes only by Central Document Room staff• DMF entered into database, assigned a number and acknowledgment letter sent to holder• A DMF is neither approved or disapproved

• Accessing the DMF: Letter of Authorization (LOA)• The DMF will be reviewed only when it is referenced in an Application or another DMF• The Holder must submit a two copies of the LOA to the DMF, plus a copy to the Applicant• The Applicant submits a copy of the LOA in their Application• The LOA is the only mechanism to trigger a review of the DMF by the FDA• LOA Template

• DMF Review Procedure• The DMF is reviewed only if referenced by an Applicant or another DMF • If the reviewer finds deficiencies in the DMF, the deficiencies are detailed in a letter to the Holder• The Applicant will be notified that deficiencies exist, but the nature of the deficiencies are not communicated to the Applicant

DMF

Types of DMF:

• Type I: Manufacturing Site, Facilities, Operating Procedures, and PersonnelNo longer accepted by the FDA (as of January 2000)

• Type II – Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product

• Type III – Packaging

• Type IV – Excipients, Colorant, Flavor, Essence, or Material Used in Their Preparation

• Type V – FDA Accepted Reference InformationUsed for sterile manufacturing plants and contract facilities for biotech products

DMF

Requirements:

Each DMF submission should contain 1. a transmittal letter, 2. administrative information about the submission, and 3. the specific information to be included in the DMF

• The DMF must be in the English language. Whenever a submission contains information in another language, an accurate certified English translation must also be included.

• Each page of each copy of the DMF should be dated and consecutively numbered. An updated table of contents should be included with each submission.

• Module 1

DMF

  Original Submissions 

Amendments 

Transmittal Letters

(Cover letter)

a. Identification of submission: Original, the type of DMF, and its subject.

b. Identification of the applications, if known, that the DMF is intended to support, including the name and address of each sponsor, applicant, or holder, and all relevant document numbers.

c. Signature of the holder or the authorized representative.

d. Typewritten name and title of the signer.

a. Identification of submission: Amendment, the DMF number, type of DMF, and the subject of the amendment.

b. A description of the purpose of submission, e.g., update, revised formula, or revised process.

c. Signature of the holder or the authorized representative.

d. Typewritten name and title of the signer.

DMF

Original Submissions AmendmentsAdministrative Information

 

a. Names and addresses of the following:

(1) DMF holder.

(2) Corporate headquarters.

(3) Manufacturing/processing facility.

(4) Contact for FDA correspondence.

(5) Agent(s), if any.

b. The specific responsibilities of each person listed in any of the categories in Section a.

c. Statement of commitment.

A signed statement by the holder certifying that the DMF is current and that the DMF holder will comply with the statements made in it.

a. Name of DMF holder.

b. DMF number.

c. Name and address for correspondence.

d. Affected section and/or page numbers of the DMF.

e. The name and address of each person whose IND, NDA, ANDA, DMF, or Export Application relies on the subject of the amendment for support.

f. The number of each IND, NDA, ANDA, DMF, and Export Application that relies on the subject of the amendment for support, if known.

g. Particular items within the IND, NDA, ANDA, DMF, and Export Application that are affected, if known.

DMF

Specific information

For M2-M3:

• EU ASMF Sample submission

DMF

• Few Updates:• May 5, 2017 all DMF Submissions must be in electronic, eCTD format

• There is NO requirement to resubmit anything that has already been submitted in paper • Resubmitting entire DMF upon conversion to eCTD, is acceptable but is NOT required • Use either version of eCTD Module 1 (DTD version 2.3 or 3.3)

• Types of Submissions Exempted

• INDs for Non Commercial Products

• Investigator-sponsored INDs • Expanded access INDs (e.g., emergency use INDs, treatment INDs)

• Blood and blood components, including Source Plasma • Devices Regulated by CBER

DMF

TIPS:• Must submit electronic submissions using the eCTD version currently supported by FDA.• Must obtain a pre-assigned application number by contacting the appropriate Center. • Must follow the FDA eCTD technical specification Table of Contents Headings and Hierarchy. • Must adhere to the formats and versions specified in the FDA Specifications for File Format Types Using

eCTD Specifications. • Must adhere to the FDA Portable Document Format (PDF) Specifications. • Must use the eCTD replace operation rather than submitting the file as new if a document replaces a document

previously submitted.• Must use the FDA Electronic Submission Gateway (ESG) for submissions 10 GB or smaller• Provide proper bookmarks, table of contents and hyperlinks on documents more than 5 pages long • Pages should be properly oriented • Scanned documents, including cover letters should be OCR’d prior to submitting • Provide electronic submissions point of contact for technical issues• Provide correct telephone, email or fax number for rejection notices

DMF

• Cover letter should always have US agent information• Leaf titles of documents should be clear and indicative of the document • Cover letters should include the sequence number and if possible, date of submission (e.g. coverletter-0004-

Jan-31-2017) • Leaf titles for all annual report documents should include the reporting period (e.g. “AR-specifications-Feb-

01-2016-Jan-31-2017). That way, reviewers can differentiate between one year’s report from another. • Do not include form 356h when submitting via gateway. DMFs are automatically processed without the form• Choose “CDER” as the center and “eCTD” as the submission type, when transmitting via ESG • When transitioning from paper to eCTD and sponsor is utilizing v2.01 DTD, use “original-application” as the

submission type. Subsequent submissions will be coded as “amendment”. • When transitioning from paper to eCTD utilizing and sponsor is utilizing v3.3 DTD, the submission-Id

should always be the same as the eCTD sequence number. (e.g. 0034-submission id-“original application”- sub-type-“application”-sequence number-“0034”; 0035-submission-id-“original application”- sub-type-“application”-sequence number-“0035).

• Be sure to apply the correct metadata for m3.2.p and/or m3.2.s eCTD sections for every submission. Any minor change will add another 3.2.p. and/or 3.2.s section thus, creating duplicate sections

DMF

Thankyou